The longterm objective of the PI is to study the role of lipoprotein and cell membrane fluidity in the development and regression of atherosclerosis. The present proposal specifically focuses on the metabolism of molecular species of lecithin as influenced by the plasma lecithin-cholesterol acyltransferase (LCAT) and lysolecithin acyltransferase (LAT), and on the role of disaturated lecithins (DSL) in atherogenesis. Evidence for the operation of LAT reaction in vivo will be obtained from the studies on the acylation of LDL-bound lysolecithin to lecithin in plasma of rabbits in vivo. The physiological consequences of the reaction will be studied by analyzing the molecular species composition of lecithins in abetalipoproteinemic plasma after the in vitro stimulation of LAT by the addition of LDL. The enzyme's role in the production of DSL will be tested by determining the DSL levels in patients known to have high LAT activities. The specificity of LCAT towards various molecular species of lecithin will be studied by analysis of the lecithin composition before and after the LCAT reaction in whole plasma. The reason why disproportionately more saturated fatty acids are transferred to cholesterol will be investigated by studying the effect of various apoprotein activators on the composition of cholesterol esters formed. The lecithin/free cholesterol ratio, lecithin/sphingomyelin ratio, and the DSL concentration of the plasma will be estimated in patients with angiographic evidence of atherosclerosis to determine which of these parameters is a better indicator of the disease. The suitability of using the saturation of 2-position of lecithin as a biochemical marker for the presence of atherosclerosis will be studied. The possible mechanisms by which DSL influence the atherogenesis will be studied by their effect on the metabolism of LDL, HDL, and the platelets. The effect of DSL enrichment of LDL on its binding, uptake and degradation by fibroblasts in culture, and on its fractional catabolic rate in vivo will be determined. In addition, the effect of DSL enrichment of HDL on the HDL-induced cholesterol efflux from the cultured cells will be studied. The effect of DSL incorporation into platelets on the sensitivity of the platelets to aggregating agents, and on the prostaglandin synthesis will be studied. All these studies should enable us to better understand the biochemical mechanisms involved in atherogenesis.